Glucose restriction delays senescence and promotes proliferation of HUVECs via the AMPK/SIRT1-FOXA3-Beclin1 pathway

Brucellosis is one of the most common global zoonoses and is caused by facultative intracellular bacteria of the genus Brucella . Numerous studies have found that MyD88 signaling contributes to protection against Brucella , however the underlying mechanism has not been entirely defined. Here we show that MyD88 signaling in hematopoietic cells contributes both to inflammation and to control of Brucella melitensis infection in vivo . While the protective role of MyD88 in Brucella infection has often been attributed to promotion of IFN-γ production, we found that MyD88 signaling restricts host colonization by B. melitensis even in the absence of IFN-γ. In vitro , we show that MyD88 promotes macrophage glycolysis in response to B. melitensis . Interestingly, a B. melitensis mutant lacking the glucose transporter, GluP, was more highly attenuated in MyD88 -/- than in WT mice, suggesting MyD88 deficiency results in an increased availability of glucose in vivo which Brucella can exploit via GluP. Metabolite profiling of macrophages identified several metabolites regulated by MyD88 in response to B. melitensis , including itaconate. Subsequently, we found that itaconate has antibacterial effects against Brucella and also regulates the production of pro-inflammatory cytokines in B. melitensis -infected macrophages. Mice lacking the ability to produce itaconate were also more susceptible to B. melitensis in vivo . Collectively, our findings indicate that MyD88-dependent changes in host metabolism contribute to control of Brucella infection.

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Relationship between proliferation and glucose metabolism in primary cultures of rabbit proximal tubules

AJP Cell Physiology ◽

10.1152/ajpcell.1990.259.3.c455 ◽

1990 ◽

Vol 259 (3) ◽

pp. C455-C461 ◽

Cited By ~ 13

Author(s):

M. J. Tang ◽

R. L. Tannen

Keyword(s):

Protein Content ◽

Cellular Proliferation ◽

Primary Cultures ◽

Glucose Consumption ◽

Cell Number ◽

Glycolytic Enzyme ◽

Proximal Tubules ◽

Low Glucose ◽

Lactate Formation ◽

Glucose Restriction

Primary cultures of rabbit proximal tubules, which revert to a glycolytic profile as reflected by increased activity of pyruvate kinase (PK) paralleled by increased glucose consumption and lactate formation, were utilized to explore the relationship between glycolytic metabolism and proliferation. Tubules placed in serum-free, hormonally defined Dulbecco's modified Eagle's medium with 5 mM glucose exhibited logarithmic growth beginning on day 3 in culture. The increase in PK activity lagged approximately 1 day behind, suggesting that the reversion to glycolysis is a consequence of rather than a prerequisite for cellular proliferation. Tubules cultured in 0.5 mM as contrasted with 25 mM glucose exhibited heightened proliferation reflected by an increase in protein content and cell number on day 5 in culture. The heightened proliferation was accompanied by increased PK activity. On day 9, after confluency had been achieved, no differences in protein content or PK activity were detected between tubules cultured in different glucose concentrations. These findings indicate that a low glucose concentration is mitogenic for renal proximal tubules and that the proliferative process in some fashion up-regulates the activity of the glycolytic enzyme PK. Furthermore, because accelerated growth proceeds in the presence of glucose restriction, the energy from glycolysis is not required for the proliferative process.

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Glucose Restriction Combined with Autophagy Inhibition and Chemotherapy in HCT 116 Spheroids Decreases Cell Clonogenicity and Viability Regulated by Tumor Suppressor Genes

Journal of Proteome Research ◽

10.1021/acs.jproteome.7b00293 ◽

2017 ◽

Vol 16 (8) ◽

pp. 3009-3018 ◽

Cited By ~ 13

Author(s):

Monica M. Schroll ◽

Gabriel J. LaBonia ◽

Katelyn R. Ludwig ◽

Amanda B. Hummon

Keyword(s):

Tumor Suppressor ◽

Tumor Suppressor Genes ◽

Suppressor Genes ◽

Hct 116 ◽

Glucose Restriction ◽

Autophagy Inhibition

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Glucose-restriction increasesTrichomonas vaginaliscellular damage towards HeLa cells and proteolytic activity of cysteine proteinases (CPs), such as TvCP2

Parasitology ◽

10.1017/s0031182019000209 ◽

2019 ◽

Vol 146 (9) ◽

pp. 1156-1166 ◽

Cited By ~ 2

Author(s):

Jesús F. T. Miranda-Ozuna ◽

Luis Alberto Rivera-Rivas ◽

Rosa Elena Cárdenas-Guerra ◽

Mar Sarai Hernández-García ◽

Sarahí Rodríguez-Cruz ◽

...

Keyword(s):

Proteolytic Activity ◽

Hela Cells ◽

Trichomonas Vaginalis ◽

Host Cells ◽

Cellular Damage ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Cell Monolayers ◽

Glucose Restriction ◽

Effect Of Glucose

AbstractTrichomonas vaginalisinduces cellular damage to the host cells (cytotoxicity) through the proteolytic activity of multiple proteinases of the cysteine type (CPs). Some CPs are modulated by environmental factors such as iron, zinc, polyamines, etc. Thus, the goal of this study was to assess the effect of glucose onT. vaginaliscytotoxicity, proteolytic activity and the particular role of TvCP2 (TVAG_057000) during cellular damage. Cytotoxicity assays showed that glucose-restriction (GR) promotes the highest HeLa cell monolayers destruction (~95%) by trichomonads compared to those grown under high glucose (~44%) condition. Zymography and Western blot using different primary antibodies showed that GR increased the proteolytic activity, amount and secretion of certain CPs, including TvCP2. We further characterized the effect of glucose on TvCP2. TvCP2 increases in GR, localized in vesicles close to the plasma membrane and on the surface ofT. vaginalis. Furthermore, pretreatment of GR-trichomonads with an anti-TvCP2r polyclonal antibody specifically reduced the levels of cytotoxicity and apoptosis induction to HeLa cells in a concentration-dependent manner. In conclusion, our data show that GR, as a nutritional stress condition, promotes trichomonal cytotoxicity to the host cells, increases trichomonad proteolytic activity and amount of CPs, such as TvCP2 involved in cellular damage.

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